Human astrovirus capsid protein releases a membrane lytic peptide upon trypsin maturation

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dc.citation.articleNumbere00802-23en_US
dc.citation.issueNumber8en_US
dc.citation.journalTitleJournal of Virologyen_US
dc.citation.volumeNumber97en_US
dc.contributor.authorYkema, Matthewen_US
dc.contributor.authorYe, Kaien_US
dc.contributor.authorXun, Mengen_US
dc.contributor.authorHarper, Justinen_US
dc.contributor.authorBetancourt-Solis, Miguel A.en_US
dc.contributor.authorArias, Carlos F.en_US
dc.contributor.authorMcNew, James A.en_US
dc.contributor.authorTao, Yizhi Janeen_US
dc.date.accessioned2024-05-03T15:51:11Zen_US
dc.date.available2024-05-03T15:51:11Zen_US
dc.date.issued2023en_US
dc.description.abstractThe human astrovirus (HAstV) is a non-enveloped, single-stranded RNA virus that is a common cause of gastroenteritis. Most non-enveloped viruses use membrane disruption to deliver the viral genome into a host cell after virus uptake. The virus–host factors that allow for HAstV cell entry are currently unknown but thought to be associated with the host-protease-mediated viral maturation. Using in vitro liposome disruption analysis, we identified a trypsin-dependent lipid disruption activity in the capsid protein of HAstV serotype 8. This function was further localized to the P1 domain of the viral capsid core, which was both necessary and sufficient for membrane disruption. Site-directed mutagenesis identified a cluster of four trypsin cleavage sites necessary to retain the lipid disruption activity, which is likely attributed to a short stretch of sequence ending at arginine 313 based on mass spectrometry of liposome-associated peptides. The membrane disruption activity was conserved across several other HAstVs, including the emerging VA2 strain, and effective against a wide range of lipid identities. This work provides key functional insight into the protease maturation process essential to HAstV infectivity and presents a method to investigate membrane penetration by non-enveloped viruses in vitro.en_US
dc.identifier.citationYkema, M., Ye, K., Xun, M., Harper, J., Betancourt-Solis, M. A., Arias, C. F., McNew, J. A., & Tao, Y. J. (2023). Human astrovirus capsid protein releases a membrane lytic peptide upon trypsin maturation. Journal of Virology, 97(8), e00802-23. https://doi.org/10.1128/jvi.00802-23en_US
dc.identifier.digitalhuman-astrovirus-capsid-proteinen_US
dc.identifier.doihttps://doi.org/10.1128/jvi.00802-23en_US
dc.identifier.urihttps://hdl.handle.net/1911/115555en_US
dc.language.isoengen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleHuman astrovirus capsid protein releases a membrane lytic peptide upon trypsin maturationen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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